Association between diffuse idiopathic skeletal hyperostosis and intestinal microbiota dysbiosis: a case-control study

Abstract

Background: Diffuse Idiopathic Skeletal Hyperostosis (DISH) is a chronic disease with unknown pathogenesis and no specific treatment, which is known to cause axial stiffness and increase the risk of severe spinal fractures with neurological involvement after minor trauma. Although DISH has traditionally been considered a metabolic disease, more recent studies have observed that an inflammatory background may be involved in its development. Dysbiosis has been linked to the development of multiple inflammatory diseases such as inflammatory bowel disease or axial spondylarthritis. As such, were DISH to also be linked to dysbiosis, novel preventive strategies could be developed. Objectives: the main aim of this study is to analyse the association between gut microbiota dysbiosis and DISH. The secondary objectives include determining which microorganisms could be responsible for the expected gut microbiota dysbiosis in DISH patients, whether said dysbiosis is independent of the presence or absence of metabolic diseases, and if dysbiosis is present in all DISH radiographic phenotypes. Study design: this study is designed as a multicentric case-control study. It will be led by the “Hospital Universitari Doctor Josep Trueta” of Girona with the collaboration of 9 other Catalan hospitals, over a period of 2 years and 7 months Participants and methods: a sample of 185 cases and 370 controls matched by age and sex will be recruited over a period of 11 months using non-probabilistic consecutive sampling for cases and probabilistic random sampling for controls. Microbiota composition will be determined in faecal samples using 16S rRNA gene sequencing, and principal component analysis will then be performed in order to design a dysbiosis test algorithm which will discriminate between presence or absence of dysbiosis in both cases and controls. Radiograph images of DISH patients will be analysed to determine their radiographic pattern. All other variables will be collected either from the medical record, anamnesis or measured at the consult. Once all samples have been collected, the data will be analysed using logistic regressions and multinominal logistic regressions to adjust for all covariables